• We've upgraded our forums. Please post any issues/requests in this thread.

Don't Kill Bacteria, Disable It.

Kreij

Senior Monkey Moderator
Staff member
Joined
Feb 6, 2007
Messages
13,817 (3.48/day)
Likes
5,524
Location
Cheeseland (Wisconsin, USA)
Processor Intel Core 2 Quad QX9650 Extreme @ 3.0 GHz
Motherboard Asus Rampage Formula
Cooling ZeroTherm Nirvana NV120 Premium
Memory 8GB (4 x 2GB) Corsair Dominator PC2-8500
Video Card(s) 2 x Sapphire Radeon HD6970
Storage 2 x Seagate Barracuda 320GB in RAID 0
Display(s) Dell 3007WFP 30" LCD (2560 x 1600)
Case Thermaltake Armor w/ 250mm Side Fan
Audio Device(s) SupremeFX 8ch Audio
Power Supply Thermaltake Toughpower 750W Modular
Software Win8 Pro x64 / Cat 12.10
#1
This is a bit long, but well worth the read ....

An antibiotic effect minus resistance

Researcher's compound disables bacteria instead of killing them

After 70 years, antibiotics are still the primary treatment for halting the spread of bacterial infections. But the prevalence of antibiotic resistance is now outpacing the rate of new drug discovery and approval.

A microbiologist at the University of Wisconsin-Milwaukee (UWM) has discovered a different approach: Instead of killing the bacteria, why not disarm them, quashing disease without the worry of antibiotic resistance?

Ching-Hong Yang, associate professor of biological sciences, has developed a compound that shuts off the "valve" in a pathogen's DNA that allows it to invade and infect.

The research is so promising that two private companies are testing it with an eye toward commercialization.

"We analyzed the genomic defense pathways in plants to identify all the precursors to infection," says Yang. "Then we used the information to discover a group of novel small molecules that interrupt one channel in the intricate pathway system."

Yang and collaborator Xin Chen, a professor of chemistry at Changzhou University in China, have tested the compound on two virulent bacteria that affect plants and one that attacks humans. They found it effective against all three and believe the compound can be applied to treatments for plants, animals and people.

The work was published online this month in the journal Antimicrobial Agents and Chemotherapy.

Urgent concerns about antibiotics

The economic costs and health threats of antibiotic resistance have become so serious that the World Health Organization (WHO) this year dedicated World Health Day to call global attention to the issue.

Antibiotics are routinely sprayed on crops and widely used in factory farming of animals, which causes resistance to develop quickly. That antibiotic resistance is then transferred to humans who eat the food containing antibiotic-resistant bacteria.

Among the bacteria tested by the researchers is Pseudomonas aeruginosa, which is resistant to a broad range of antibiotics. It causes infections in people with compromised immune systems, such as HIV and cancer patients. It's also responsible for lung infections in patients with cystic fibrosis, and hospital-related infections such as urinary tract infections, pneumonia and infections from burns.

The fatality rate from these is about 50 percent. Hospital-acquired urinary tract infections by P. aeruginosa alone cost more than $3.5 billion a year in the U.S.

Road to the market

The research has attracted interest from two companies. Creative Antibiotics, a Swedish pharmaceutical company, is testing the compound and derivatives for human therapeutic uses and Wilbur-Ellis Agribusiness Division, based in Washington and California, is examining them for agricultural uses.

Despite the constant threat of disease in agriculture, says John Frieden, a biologist and R&D manager with Wilbur-Ellis, the industry has not had access to any new antibiotics in many years. U.S. regulatory agencies do not allow agribusiness to use antibiotics that are also used for human health – even if they would be effective.

"The thing that caught my attention," Frieden says, "was that this was not an antibiotic, but it accomplishes the same thing as an antibiotic."

Although he says it is too soon to tell if a product could spring from the research, the approach is "incredibly unique. I've never seen anything that is even close to a commercial application like this. It could be very big."

The researchers have filed two patents on the work through the UWM Research Foundation (UWMRF), and Yang is partially funded through two UWMRF Bradley Catalyst Grants and a UWM Research Growth Initiative (RGI) grant.

Virulence factors

The compounds Yang and Chen have developed are unique because they take aim at one component of a cluster that makes pathogenic bacteria harmful.

One of those components, the type III secretion system (T3SS), gives pathogens their ability to invade a cell, letting in a host of proteins that enhance the bacterium's ability to cause disease.

"These bacteria are very smart," says Yang. "They grow a narrow appendage that acts as a 'needle,' injecting the virulence factors, such as toxins, into the host cell. The host cell cannot recognize the pathogen's 'needle,' so its defense mechanism is not triggered."

Yang and Chen's compounds block the production of T3SS. Although they have tested the compounds on only three pathogens, they have reason to believe the compounds will be effective against far more.

"T3SS exists in many different kinds of disease-causing bacteria," says Yang, "so the compounds can target multiple pathogens. That's the beauty of it."

He and his lab members are now working on developing more derivatives that could be effective against different kinds of harmful bacteria.

Yang also believes that their therapeutic compounds, like antibiotics, can offer both a broad spectrum of activity and be unique to a specific pathogen, depending on which virulence elements are targeted.
 
Joined
Sep 21, 2011
Messages
499 (0.22/day)
Likes
119
System Name Multipurpose desktop
Processor AMD Phenom II x6 1605T @ 3.75Ghz , NB @ 2.5
Motherboard Gigabyte 990FXA-UD3 (rev 1.0)
Cooling Prolimatech Megahalems Rev. C, 2x120mm CM Blademaster
Memory Corsair Vengeance LP (4x4GB) @1666Mhz 9-9-9-20-24 1T
Video Card(s) ASUS Strix R7-370 4GB OC
Storage 2x WD Caviar Black 500GB Sata III in RAID 0
Display(s) Acer S211HL 21.5" 1920x1080
Case Cooler Master Centurion 534+, 3x 120mm CM Sickle Flow
Power Supply Seasonic X650 Gold
Software Windows 7 x64 Home Premium SP1
#2
Interesting.
Looks like we're going to be saved from the antibiotic resistant bacteria. At least for a generation (or two); I wonder how long it will take for mutated bacteria, that these new methods don't affect, to take over the bacterial population and force us to come up with another method.
 

Kreij

Senior Monkey Moderator
Staff member
Joined
Feb 6, 2007
Messages
13,817 (3.48/day)
Likes
5,524
Location
Cheeseland (Wisconsin, USA)
Processor Intel Core 2 Quad QX9650 Extreme @ 3.0 GHz
Motherboard Asus Rampage Formula
Cooling ZeroTherm Nirvana NV120 Premium
Memory 8GB (4 x 2GB) Corsair Dominator PC2-8500
Video Card(s) 2 x Sapphire Radeon HD6970
Storage 2 x Seagate Barracuda 320GB in RAID 0
Display(s) Dell 3007WFP 30" LCD (2560 x 1600)
Case Thermaltake Armor w/ 250mm Side Fan
Audio Device(s) SupremeFX 8ch Audio
Power Supply Thermaltake Toughpower 750W Modular
Software Win8 Pro x64 / Cat 12.10
#3
Given the mutation rate of cellular organisms, I give it about a week. :D
 

Kreij

Senior Monkey Moderator
Staff member
Joined
Feb 6, 2007
Messages
13,817 (3.48/day)
Likes
5,524
Location
Cheeseland (Wisconsin, USA)
Processor Intel Core 2 Quad QX9650 Extreme @ 3.0 GHz
Motherboard Asus Rampage Formula
Cooling ZeroTherm Nirvana NV120 Premium
Memory 8GB (4 x 2GB) Corsair Dominator PC2-8500
Video Card(s) 2 x Sapphire Radeon HD6970
Storage 2 x Seagate Barracuda 320GB in RAID 0
Display(s) Dell 3007WFP 30" LCD (2560 x 1600)
Case Thermaltake Armor w/ 250mm Side Fan
Audio Device(s) SupremeFX 8ch Audio
Power Supply Thermaltake Toughpower 750W Modular
Software Win8 Pro x64 / Cat 12.10
#4
Here's another. Viruses, not bacteria, this time ...
Versatile inhibitor prevents viral replication

Munich, 28 October 2011

Broad-spectrum antibiotics, which are active against a whole range of bacterial pathogens, have been on the market for a long time. Comparably versatile drugs to treat viral diseases, on the other hand, have remained elusive. Using a new approach, research teams led by Dr. Albrecht von Brunn of LMU Munich and Professor Christian Drosten from the University of Bonn have identified a compound that inhibits the replication of several different viruses, including the highly aggressive SARS virus that is responsible for severe acute respiratory syndrome. The new method exploits the fact that interactions between certain host proteins and specific viral proteins are essential for viral replication. One of these host proteins is part of a signaling relay in the cell. The broad-spectrum antiviral compound used by the researchers blocks this signal pathway without having a deleterious effect on the host. “We have shown in this study that a broadly based search for new cellular targets can uncover new functional principles that have a demonstrable impact on virus replication,” says von Brunn. “We have confirmed that the approach works in cell culture. We now hope that these laboratory results can be translated into clinically effective therapies. At the very least, our high-throughput procedure can be utilized to systematically screen various protein-virus interactions as potential targets for inhibitory compounds.” The new study was carried out under the auspices of the SARS Research Network, which is supported by the Federal Ministry for Education and Research (BMBF). (PloS Pathogens, 27. October 2011)
Broad-spectrum antibiotics that inhibit the growth of various species of bacterial pathogens are well known. Virologists, unfortunately, have no comparably versatile weapons in their armory. Individual drugs that are active against different types of viral pathogens are simply not available. “All of the antiviral agents we have are directed specifically at the virus itself,” explains Professor Christian Drosten, Director of the Institute of Virology at Bonn University Hospital. “And since viral pathogens are highly diverse, each of these agents can attack only certain viruses.” Moreover, viruses are also highly mutable, making the weaponry they can deploy against us even more powerful. What works against one viral strain may be essentially useless against another.

The SARS virus, a previously unknown pathogen which threatened to cause a worldwide pandemic in 2003, has spurred on the search for new antiviral substances. Only recently, it was shown that not only Chinese, but also European, bats carry the SARS virus. “But in contrast to the situation with bird influenza, one cannot simply kill these free-living animals in order to eradicate the pathogen,” says Drosten. “That would have catastrophic ecological consequences and, apart from that, bats are retiring and secretive in their habits.” If one wishes to develop drugs against viruses that can “hide” in animal species, one must explore other alternatives.

The research teams assembled by von Brunn and Drosten have now discovered a way to prevent the replication of a whole family of viruses by depriving them of an essential host factor. They first identified host proteins with which SARS viral proteins interact. This strategy led to the finding that a cellular signaling pathway is essential for the replication not only of the SARS virus, but also of a whole set of related viruses that are pathogenic to humans and animals.

“This signal pathway is normally involved in regulating the immune system,” says Drosten. “We used a substance that inhibits the function of one of the proteins in the pathway, and found that it suppresses viral replication.” In other words, drugs that block this pathway inhibit the replication of many different viruses, and therefore act as broad-spectrum antivirals. This opens a route to the treatment of conditions caused by the SARS virus, but also a whole variety of human coronaviruses, and pathogens that infect the internal organs of chickens, pigs and cats. Inhibition of this pathway does not damage the host, because parallel pathways can compensate for its normal role in the cell.

The successful inhibition of virus replication was not a result of serendipity. The researchers in Munich have developed a technique that allows them to systematically probe different proteins for the ability to interact with defined targets. “In order to replicate in the body of its host, a virus must first gain entry to a suitable cell type by binding to a specific receptor protein on its surface,” says von Brunn, who works in the Max von Pettenkofer Institute at LMU Munich. “We have used an automated, high-throughput process to systematically test various protein-virus combinations as potential targets for possible inhibitors. The success of this strategy proves that a broadly based search for cellular targets can uncover new functional principles that have a demonstrable impact on virus replication,” says von Brunn.

The investigators have shown in cell cultures that their approach actually works. “However, it will be years before we know whether or not these results can be translated into effective treatments,” Drosten says. The study also underlines the importance of research collaborations. Drosten is convinced that “neither group could have done this on its own”. The SARS Research Network, which is coordinated by Drosten, brings together virological expertise from six university institutes, two veterinary and four medical, located in Hannover, Gießen, Marburg, Bonn, Munich and St. Gallen (Switzerland). (University of Bonn)
 
Joined
Dec 6, 2005
Messages
9,810 (2.23/day)
Likes
3,798
Location
Manchester, NH
System Name Working on it ;)
Processor I7-4790K
Motherboard MSI Z97
Cooling Be Quiet Pure Rock Air
Memory 16GB 4x4 G.Skill CAS9 2133 Sniper
Video Card(s) Intel IGP (Dedicated GPU TBD)
Storage WD 320 / 500KS / 500KS / 640KS / 640LS / 640LS / 640LS / 1TBFAEX and a NAS with 2x2Tb WD Black
Display(s) 24" DELL 2405FPW
Case Rosewill Challenger
Audio Device(s) Onboard + HD HDMI
Power Supply Corsair HX750 (love it)
Mouse Logitech G5
Software Win 7 Pro
#5
Given the mutation rate of cellular organisms, I give it about a week. :D
About two years ago on NHPR, a woman researcher was speaking about how bacteria "attack" a host.

Short story... bacteria produce toxins to damage the host BUT... only after the colony of bacteria had reached significant enough number/size where a chemical message is triggered that tells the bacteria to release the toxins. In other words, most bacteria are harmless until they reach a critical mass. It makes sense. If they weren't numerous enough, they wouldn't be able to stage enough of an attack to weaken the host and sufficiently keep multipling.

So this woman was working on a means to negate that chemical message. The bacteria wouldn't do much harm to the host and give the host time to kill off the bacteria by natural means.

But, she ended the talk by saying that the bacteria would certainly evolve some resitance, as they always do.

Microphages, anyone?
 
Joined
Sep 21, 2011
Messages
499 (0.22/day)
Likes
119
System Name Multipurpose desktop
Processor AMD Phenom II x6 1605T @ 3.75Ghz , NB @ 2.5
Motherboard Gigabyte 990FXA-UD3 (rev 1.0)
Cooling Prolimatech Megahalems Rev. C, 2x120mm CM Blademaster
Memory Corsair Vengeance LP (4x4GB) @1666Mhz 9-9-9-20-24 1T
Video Card(s) ASUS Strix R7-370 4GB OC
Storage 2x WD Caviar Black 500GB Sata III in RAID 0
Display(s) Acer S211HL 21.5" 1920x1080
Case Cooler Master Centurion 534+, 3x 120mm CM Sickle Flow
Power Supply Seasonic X650 Gold
Software Windows 7 x64 Home Premium SP1
#6
Inhibition of this pathway does not damage the host, because parallel pathways can compensate for its normal role in the cell.
That worries me. How do they know it won't have some kind of systemic effect they're not immediately aware of?
They need to do some testing.
 
Joined
Jul 30, 2007
Messages
6,560 (1.73/day)
Likes
835
System Name Vintage
Processor i7 - 3770K @ Stock
Cooling Scythe Zipang II
Memory 2x4GB Crucial DDR3
Video Card(s) MSI GTX970
Storage M4 124GB SSD// WD Black 640GB// WD Black 1TB//Samsung F3 1.5TB
Display(s) Samsung SM223BW 21.6"
Case Generic
Power Supply Corsair HX 520W
Software Windows 7
#7
Given the mutation rate of cellular organisms, I give it about a week. :D
Finally someone who understands genetic changes in a reproducing organism